The purpose of these studies will be to determine how the synthesis and degradation of apoprotein-B, a component of very low density (VLDL), intermediate density (IDL) and low density lipoproteins (LDL), is regulated. Because apo-B is secreted from the liver (along with triglyceride (TG) and cholesterol as a component of VLDL, and remains intact until LDL is removed from the circulation, study of the factors controlling its synthesis and degradation will yield important information relevant to lipid and lipoprotein metabolism. The studies will involve normal subjects and individuals with varying lipid disorders. Dietary and drug regimens will be employed to alter plasma TG and cholesterol levels in the subjects. Apoprotein-B metabolism will be studied in each subject under baseline conditions and during one of the perturbations. During the past year we have completed weight reduction studies on three hyperlipidemic individuals, baseline studies on five normal subjects, studies of lipoprotein turnover in five patients with myeloproliferative diseases and studies both pre- and post-portocaval shunt in a hyperlipidemic man. The results are under analysis.